A novel androgen-regulated gene, PMEPA1, located on chromosome 20q13 exhibits high level expression in prostate

Biologic effects of androgen on target cells are mediated in part by transc riptional regulation of androgen-regulated genes (ARGs) by androgen recepto r. Using serial analysis of gene expression (SAGE), we have identified a co mprehensive repertoire of ARGs in LNCaP cells, One of the SAGE-derived tags exhibiting homology to an expressed sequence tag was maximally induced in response to synthetic androgen R1881 treatment, The open reading frame of t he androgen induced RNA (PMEPA1) was characterized as a 759-bp nucleotide s equence coding for a 252-amino-acid protein. The analysis of PMEPA1 protein sequence indicated the existence of a type Ib transmembrane domain between residues 9 and 25. Analysis of multiple-tissue Northern blots revealed the highest level of PMEPA1 expression in prostate tissue. PMEPA1 expression w as predominately detected in glandular epithelial cells of prostate by in s itu hybridization analysis, The expression of PMEPA1 in LNCaP cells was ind uced by androgen in a time- and dose-specific manner. Evaluation of PMEPA1 expression in androgen-dependent/independent tumors of the CWR22 xenograft model revealed that PMEPA1 was overexpressed in three of four androgen-inde pendent tumor tissues. These observations define PMEPA1 as a novel androgen -regulated gene exhibiting abundant expression in prostate tissue. The incr eased expression of PMEPA1 in relapsed tumors of the CWR22 model suggests a ctivation of androgen signaling in hormone refractory disease. PMEPA1, alon g with other highly androgen-induced prostate-specific genes, has potential to serve as an androgen signaling read-out biomarker in prostate tissue. ( C) 2000 Academic Press.